Is LRBA p.Arg167= (c.501C>T) pathogenic?

LRBA p.Arg167= (c.501C>T) is classified Likely benign in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-14). Very rare (popmax 0.00549%, sas); Associated with combined immunodeficiency due to LRBA deficiency.

What condition is associated with LRBA p.Arg167= (c.501C>T)?

LRBA p.Arg167= (c.501C>T) is associated with combined immunodeficiency due to LRBA deficiency (ClinVar).

How common is LRBA p.Arg167= (c.501C>T) in the general population?

LRBA p.Arg167= (c.501C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

LRBA p.Arg167=

Q: How is Syndromic autoimmune enteropathy due to LRBA deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.501C>T · rs763929621 · VCV641591

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

combined immunodeficiency due to LRBA deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -5.4, phastCons 0.68
Overall
CADD	6.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,042 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000992% 16/1,613,546 alleles · very rare exomes 14/1,461,548 · genomes 2/151,998 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,208
East Asian	0.00446%	22,426
Remaining individualsnot grpmax-eligible	0.0032%	31,234
Admixed American	0.00167%	59,950
African / African-American	0.00134%	74,840
European (non-Finnish)	0.000424%	235,963

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: LRBA
Protein: p.Arg167=
Coding: c.501C>T
MANE Select: NM_001364905
dbSNP: rs763929621
Type: single nucleotide variant
Location: chr4:150928564 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)

Full LRBA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to LRBA deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Syndromic autoimmune enteropathy due to LRBA deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

LRBA p.Arg167Cys Uncertain significance ★★ same residue
LRBA p.Arg167Ser Uncertain significance ★★ ⚠ same residue
LRBA p.Arg167His Uncertain significance ★ ⚠ same residue
LRBA p.Arg167Gly Uncertain significance ★ same residue
MAB21L2 p.Val167Ala Uncertain significance ★ ⚠ same residue
LRBA c.216+1G>C Pathogenic/Likely pathogenic ★★ same condition
LRBA c.2259-2A>G Likely pathogenic ★★ same condition
LRBA c.2767-2A>G Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lrba-p-arg167 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown